In order to develop a rational therapy for BPH, we propose to study the pathogenesis of this disorder by measuring the intracellular hormone environment in the prostate. Such studies will include assay of levels of endogenous T, DHT, androstanediols, and delta4-andro-stenedione in the prostate, as well as identification of the amount and type of steroid bound to the cytosol receptor protein. Comparison of such data from normals and patients with BPH should afford insight into pathogenetic mechanisms. The effects of anti-androgens, drugs shown to be clinically effective in BPH, on androgen metabolism and binding will also be studied to search for a biochemical correlant of the biological effects of such agents. The effect of estrogen on the intracellular hormone environment and the presence of estrogen cytosol receptor and estrogen metabolites in the prostate will be measured. The clinical responsiveness of prostate cancer to androgen ablation will be retro-spectively correlated with levels of endogenous DHT and cytosol receptor protein in a prostate biopsy prior to therapy. Such studies will provide evidence for the feasibility of predicting prostate cancer differentiation by biochemical analysis of a biopsy.